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A Phase 2 Blinded, Placebo-Controlled Study to Assess the Safety, Tolerability, and Efficacy of MYD-0124 to Adult Patients with Myotonic Dystrophy Type 1 (MYD-0124 Study)

Safety and Efficacy Trial of MYD-0124 for Myotonic Dystrophy Type 1

30

Average age (SD)38.1(8.9)years, Average BW (SD)57.0(8.6)kg Male 13,Female 1 ,Low-dose12 cases, high-dose12 cases, placebo6 cases

A total of 30 participants was enrolled. The first patient was enrolled on Nov 2019 and Follow up for last patient was ended on Jan 2022.

We observed 35 adverse events (AE) in 18 patients, that included low dose group of 12 events in 6 patients (50.0%) out of 12 patients, high dose group of 18 events in 9 patients out of 12 patients (75.0%), and placebo group of 5 cases (50.0%) in 3 patients out of 6 patients. AE that we could not determine cause effect relationship of the drug were 10 events in 9 subjects; in the low-dose group, diarrhea in 1 patient (8.3%), liver dysfunction in 1 patient (8.3%), and anemia in 1 patient (8.3%). ) 1 case, hypocalcemia in 1 case (8.3%) in 1 case, diarrhea in 1 case (8.3%) in the high-dose group in 1 case, abdominal discomfort in 1 case (8.3%) in 1 case, constipation in 1 case (8.3%) 1 case, flatulence 1 case (8.3%) 1 case, liver dysfunction 1 case (8.3%) 1 case, placebo group 6 cases, liver dysfunction 1 case (16.7%) 1 case). As for severe adverse event, pneumoniae was observed in 1 case (16.7%) in placebo group.

Regarding the safety of MYD-0124, the primary endpoint of the study, there were no notable safety issues observed. When the study drug was administered orally to patients with myotonic dystrophy twice daily (500 mg or 800 mg of erythromycin per day) for 24 weeks, both in the morning and evening, there were no clinically relevant events, and no new safety concerns emerged. Additionally, there were no observed tolerability problems. No statistically significant differences were found in secondary endpoints, including improvements in splicing abnormalities in skeletal muscle, myotonia score, muscle strength evaluated with a myotometer, walking distance in a 6-minute walk, and creatine kinase level, among others.

Patients with myotonic dystrophy experienced no issues with tolerating MYD-0124 treatment. While no statistically significant differences in efficacy endpoints were evident, the improvement in splicing biomarkers and the reduction in CK levels suggested that MYD-0124 might be effective for patients with myotonic dystrophy.

Jan. 10, 2024

Dec. 26, 2023

https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(23)00567-9/fulltext

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2051190069

Nakamori Masayuki

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka 565-0871, Japan

mnakamor@neurol.med.osaka-u.ac.jp

Nakamori Masayuki

Osaka University Hospital

2-15 Yamadaoka, Suita, Osaka 565-0871, Japan

+81-6-6879-3571

mnakamor@neurol.med.osaka-u.ac.jp

Complete

Nov. 01, 2019

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

1. Males or females aged 20 to 55 years old at the time of informed consent
2. Genetic confirmation of DM1
3. Ambulatory (orthoses allowed, canes and walkers not allowed) and able to walk at least 25 meters at screening

1. Treatment with macrolide antibiotics medication within 60 days prior to screening.
2. Clinically significant abnormal ECG or significant symptoms of cardiac dysfunction at Screening
3. Intellectual disability, or significant behavioral neuropsychiatric manifestations
4. Clinically significant abnormalities in screening laboratory values that would render the subject unsuitable for inclusion
5. Treatment with anti-myotonia medication within 30 days prior to screening. May include, but not be limited to: Phenytoin, Carbamazepine, Procainamide, Mexiletine
6. Recent history of or current drug or alcohol abuse
7. Have any condition, which, in the opinion of the investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the study

Both

Myotonic Dystrophy Type 1

Placebo, MYD-0124 500 mg/day, or 800 mg/day is administrated orally over the course of 24 weeks.

Myotonic dystrophy, Muscular dystrophy, Erythromycin

Safety (the number of participants with adverse events)

1. Mean Change from Baseline in Splicing Abnormality .
2. Mean Change From Baseline in EMG score.
3. Mean Change From Baseline in Muscle Strength.
4. Mean Change From Ambulation Using the 6 Minute Walk Distance.
5. Mean Change From Baseline in Patient-Reported Quality of Life.
6. Mean Change From Baseline in Clinical Global Impression.
7. Mean Change From Baseline in CK Value.

+81-6-6210-8290

Sept. 10, 2019

none